Bro1 binding to Snf7 regulates ESCRT-III membrane scission activity in yeast.

Bro1 binding to Snf7 regulates ESCRT-III membrane scission activity in yeast.
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DOI:
10.1083/jcb.201007018
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发表时间:
2011-01-24
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Odorizzi G
Odorizzi G
中科院分区:
其他
文献类型:
--
作者:
Wemmer M;Azmi I;West M;Davies B;Katzmann D;Odorizzi G

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泛素水解酶激活因子Bro1通过抑制Vps4介导的拆解增强ESCRT-III的稳定性。运输所需的内体分选复合体(ESCRT)促进囊泡内陷到内体的管腔,包膜病毒的萌发,以及细胞质分裂过程中细胞的分离。这些过程共享一个拓扑学上相似的膜断裂事件,由ESCRT-III在膜的胞浆表面组装促进。酵母中ESCRT-III的Snf7亚基直接与辅助蛋白Bro1结合。与ESCRT-III一样,Bro1在内小体形成腔内小泡中是必需的,但它在膜断裂中的作用尚不清楚。我们表明,过表达的Bro1或其N端的Bro1结构域与Snf7结合,在体内和体外通过抑制Vps4介导的拆解提高了ESCRT-III的稳定性。这种稳定作用与电子断层扫描观察到的腔内小泡脱离频率的降低有关,暗示Bro1是ESCRT-III分解和膜断裂活动的调节因子。
The ubiquitin hydrolase activating factor Bro1 enhances ESCRT-III stability by inhibiting Vps4-mediated disassembly. Endosomal sorting complexes required for transport (ESCRTs) promote the invagination of vesicles into the lumen of endosomes, the budding of enveloped viruses, and the separation of cells during cytokinesis. These processes share a topologically similar membrane scission event facilitated by ESCRT-III assembly at the cytosolic surface of the membrane. The Snf7 subunit of ESCRT-III in yeast binds directly to an auxiliary protein, Bro1. Like ESCRT-III, Bro1 is required for the formation of intralumenal vesicles at endosomes, but its role in membrane scission is unknown. We show that overexpression of Bro1 or its N-terminal Bro1 domain that binds Snf7 enhances the stability of ESCRT-III by inhibiting Vps4-mediated disassembly in vivo and in vitro. This stabilization effect correlates with a reduced frequency in the detachment of intralumenal vesicles as observed by electron tomography, implicating Bro1 as a regulator of ESCRT-III disassembly and membrane scission activity.
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